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Cognition, 33 (1989) 25-62 2Time-locked multiregional retroactivation: A systems-level proposal for the neural substrates of recall andrecognition*ANTONIO R. DAMASIOUniversity of Iowa College of MedicineAbstractDamasio, A.R., 1989. Time-locked multiregional retroactivation: A systems-level proposal forthe neural substrates of recall and recognition. Cognition, 33: 25-62.This article outlines a theoretical framework for the understanding of the neuralbasis of memory and consciousness, at systems level. It proposes an architec-ture constituted by: (1) neuron ensembles located in multiple and separateregions of primary and first-order sensory association cortices (“early cor-tices’) and motor cortices; they contain representations of feature fragmentsinscribed as patterns of activity originally engaged by perceptuomotor interac-tions; (2) neuron ensembles located downstream from the former throughoutsingle modality cortices (local convergence zones); they inscribe amodal rec-ords of the combinatorial arrangement of feature fragments that occurred syn-chronously during the experience of entities or events in sector (1); (3) neuronensembles located downstream from the former throughout higher-order as-sociation cortices (non-local convergence zones), which inscribe amodal rec-ords of the synchronous combinatorial arrangements of local convergencezones during the experience of entities and events in sector (1); (4) feed-forwardand feedback projections interlocking reciprocally the neuron ensembles in (1)with those in (2) according to a many-to-one (feed-forward) and one-to-many(feedback) principle. Z propose that (a) recall of entities and events occurswhen the neuron ensembles in (1) are activated in time-locked fashion; (b) thesynchronous activations are directed from convergence zones in (2) and (3);and (c) the process of reactivation is triggered from firing in convergence zones*This work was supported by NINCDS grant PO1 NS19632. I thank my associates Hanna Damasio. GaryVan Hoesen, and Daniel Tranel for helping me shape many of the ideas summarized here. over the pastdecade. I also thank other colleagues who read previous versions of this manuscript over the past few yearsand made numerous helpful suggestions: Patricia Churchland. Victoria Fromkin, Jack Fromkin, EdwardKlima. Francis Crick, Terry Sejnowski, Jaques Paillard. Marge Livingstone. David Hubel, Freda Newcombe,Ursula Bellugi. Arthur Benton. Peter Eimas and Albert Galaburda. Requests for reprints should be sent toAntonio R. Damasio. Professor and Head, Department of Neurology. University of Iowa Hospitals andClinics. Iowa City, IA 52242. U.S.A.OOlO-0277/89/$11.90 0 1989, Elsevier Science Publishers B.V.26A. R. Damasioand mediated by feedback projections. This proposal rejects a single anatomi-cal site for the integration of memory and motor processes and a single storefor the meaning of entities of events. Meaning is reached by time-locked mul-tiregional retroactivation of widespread fragment records. Only the latter rec-ords can become contents of consciousness.IntroductionThis proposal describes a neural architecture capable of supporting the ex-periences that are conjured up in recall and are used for recognition, at thelevel of systems that integrate macroscopic functional regions. It arose out ofdissatisfaction with available accounts of the neural basis of higher behaviors,especially those implicit in center localizationism, behaviorism, functionalequipotentiality, and disconnection syndrome theory.The title captures the two principal notions in the proposal. First, percep-tual experience depends on neural activity in multiple regions activated simul-taneously, rather than in a single region where experiential integration wouldoccur. Second, during free recall or recall generated by perception in a recog-nition task, the multiple region activity necessary for experience occurs nearthe sensory portals and motor output sites of the system rather than at theend of an integrative processing cascade removed from inputs and outputs.Hence the term retroactivation to indicate that recall of experiences dependson reactivation close to input and output sites rather than away from them.The two critical structures in the proposed architecture are the fragmentrecord of feature-based sensory or motor activity, and the convergence zone,an amodal record of the combinatorial arrangements that bound the fragmentrecords as they occurred in experience. There are convergence zones of dif-ferent orders; for example, those that bind features into entities, and thosethat bind entities into events or sets of events, but all register combinationsof components in terms of coincidence or sequence, in space and time. Con-vergence zones are an attempt to provide an answer to the binding problem,which I see as a central issue in cognitive processing, at all taxonomic levelsand scales of operation.The adult organization described here operates on the basis ofneurobiological and reality constraints. During interactions between the per-ceivers brain and its surround, those constraints lead to a process of feature,entity, and event grouping based on physical structure similarity, spatialplacement, temporal sequence,and temporal coincidence. The records ofthose perceptuomotor interactions, both at fragment level and at combinato-rial level, are inscribed in superimposed and overlapped fashion; yet, becauseNeural substrates of recall 27The same type of neuron ensembles, operating on the same principles,constitutes the substrate for different cognitive operations, depending on thelocation of the ensemble within the system and the connections that feed intothe ensemble and that feed back out of it. Location and communication linesdetermine the topic of the neuron ensemble. The connectivity of functionalregions defines the systems-level code for cognitive processes.The neuroanatomical substrates for this organization are:(1)(2)(3)(4)primary and early association cortices, both sensory and motor, whichconstitute the substrate for feature-based records;association cortices of different orders, both sensory and motor, somelimbic structures (entorhinal cortex, hippocampus, amygdala, cingulatecortices), and the neostriatum/cerebellum, which constitute the sub-strate for convergence zones;feed-forward and feedback connectivity interrelating (1) and (2)) at mul-tiple hierarchical levels, with reciprocal patterns;non-specific thalamic nuclei, hypothalamus, basal forebrain, andbrainstem nuclei.The cognitive/neural architecture outlined above can perform: (1) percep-of the different conditions according to which they are grouped, they becomecommitted to separate neural regions. In cognitive terms I will refer to theseprocesses as domain formation (a creation of relatively separable areas ofknowledge for faces, man-made objects, music, numbers, words, socialevents, disease states, and so on), and recording of contextual complexity (arecording of the temporal and spatial interaction of entities within sets ofconcurrent events). In neural terms I will refer to these grouping processesas regionalization.tuomotor interactions with the brains surround; (2) learning of those interac-tions at the representational level defined above; (3) internal activation ofexperience-replicative representations in a recall (perception-independent)mode; (4) problem solving, decision making, planning, and creativity; and(5) communication with the evironment. All those functions are predicatedon a key operation: the attempted reconstitution of learned perceptuomotorinteractions in the form of internal recall and motor performance. Attemptedperceptuomotor reconstitution is achieved by time-locked retroactivation offragmentary records, in mutiple cortical regions as a result of feedback activ-ity from convergence zones. The success of this operation depends on atten-tion, which is defined as a critical level of activity in each of the activatedregions, below which consciousness cannot occur.According to this proposal, there is no single site for the integration ofsensory and motor processes. The experience of spatial integration is brought28A. R. Damasioabout by time-locked multiple occurrences. I thus propose a recursive, itera-tive design to substitute for the traditional unidirectional processing cascades.Although the notion of representation covers all the inscriptions related toan entity or event, that is, both fragment and binding code records, theproposal posits that only the multiregional retroactivations of the fragmentcomponents become a content of consciousness. The perceptuomotor recon-stitutions that form the substrate of consciousness thus occur in an anatomi-cally restricted sector of the cerebrum, albeit in a distributed, multiple-sitemanner.In this proposal, and unlike traditional neurological models, there is nolocalizable single store for the meaning of a given entity whithin a corticalregion. Rather, meaning is reached by widespread multiregional activationof fragmentary records pertinent to a stimulus, wherever such records maybe stored within a large array of sensory and motor structures, according toa combinatorial arrangement specific to the entity. A display of the meaningof an entity does not exist in permanent fashion. It is recreated for each newinstantiation. The same stimulus does not produce the same evocations atevery instantiation, though many of the same or similar sets of records willbe evoked in relation to thesame or comparable stimuli. The records thatpertain to a given entity are distributed in the telencephalon both in the sensethat they are inscribed over sizable synaptic populations and in the sense thatthey are to be found in multiple loci of cerebral cortex and subcortical nuclei.The proposal permits the reinterpretation of the main types of higher cog-nitive disorder - the agnosias, the amnesias, and the aphasias - and promptstestable hypotheses for further investigation of those disorders. It also pro-vides a basis for neural hypotheses regarding psychiatric conditions such associopathy, phobias and schizophrenia.Several predictions based on thisproposal are now being tested in humans, with or without focal brain lesions,using advanced imaging methods and cognitive probes. Some anatomical andphysiological aspects of the proposal can be investigated in experimentalanimals. The concept of convergence zone can be explored with computa-tional techniques.The need for temporo-spatial integration and its traditional solutionCurrent knowledge from neuroanatomy and neurophysiology of the primatenervous system indicates unequivocally that any entity or event that we nor-mally perceive through multiple sensory modalities must engage geographi-cally separate sensory modality structures of the central nervous system; Sincevirtually every conceivable perception of an entity or event also calls for aNeural substrates of recall29motor interaction on the part of the perceiver and must include the concomit-ant perception of the perceivers somatic state, it is obvious that perceptionof external reality and the attempt to record it are a multiple-siteneurophysiological affair. This notion is reinforced by the discovery, over thepast decade, of a multiplicity of subsidiary functional regions that show somerelative dedication not just to a global sensory modality or motor performancebut also to featural and dimensional aspects of stimuli (see Damasio, 1985a;Van Essen & Maunsell, 1983; Livingstone & Hubel, 1988, for a pertinentreview). The evidence from psychological studies in humans is equally com-pelling in suggesting featural fragmentation of perceptual processes (see Bar-low, 1981; Julesz, 1971; Posner, 1980; Triesman & Gelade, 1980). Earlygeographic parcellation of stimulus properties has thus grown rather thanreceded, and the condition faced by sensory and motor representations of thebrains surround is a fragmentation of the inscription of the physical structuresthat constitute reality, at virtually every scale. The physical structure of anentity (external, such as an object, or internal, such as a specific somaticstate) must be recorded in terms of separate constituent ingredients, each ofwhich is a result of secondary mappings at a lower physical scale. And thefragmentation that obtains for concrete entities is even more marked forabstract entities and events, considering that abstract entities correspond tocriterion-governed conjunctions of dimensions and features present in con-crete entities, and that events are an interplay of entities.The experience of reality, however, both in ongoing perception as well asin recall, is not parcellated at all. The normal experience we have of entitiesand events is coherent and in-register,both spatially and temporally. Fea-tures are bound in entities, and entities are bound in events. How the brainachieves such a remarkable integration starting with the fragments that it hasto work with is a critical question. I call it the binding problem (I use theterm binding in a broader sense than it has been used by Treisman andothers, to denote the requisite integration of components at all levels andscales, not only in perception but also in recall). The brain must have devicescapable of promoting the integration of fragmentary components of neuralactivity, in some sort of ensemble pattern that matches the structures ofentities, events, and relationships thereof. The solution, implicitly or overtly,has been, for decades, that the components provided by different sensoryportals are projected together in so-called multimodal cortices in which, pre-sumably, a representation of integrated reality is achieved. According to thisintuitively reasonable view, perception operates on the basis of a unidirec-tional cascade of processors, which provides, step by step, a refinement ofthe extraction of signals, first in unimodal streams and later in a sort ofmultimedia and multitrack apparatus where integration occurs. The general30A. R. Damasiodirection of the cascade is caudo-rostral, in cortical terms, and the integrativecortices are presumed to be in the anterior temporal and anterior frontalregions. Penfields findings in epileptics undergoing electrical stimulation oftemporal cortex seemed to support this traditional view (Penfield & Jasper,19.54), as did influential models of the neural substrates of cognition in the post-war period, such as Geschwinds (1965) and Lurias (1966). The major discov-eries of neurophysiology and neuroanatomy over the past two decades have alsoseemed compatible with it. On the face of it, anatomical projections doradiate from primary sensory cortices and do create multiple-stage sequencestoward structures in the hippocampus and prefrontal cortices (Jones & Pow-ell, 1970; Nauta, 1971; Pandya & Kuypers, 1969; Van Hoesen, 1982).Moreover, without a doubt, single-cell neurophysiology does suggest that,the farther away neurons are from the primary sensory cortices, the more theyhave progressively larger receptive fields and less unimodal responsivity (seeDesimone & Ungerleider, 1988, for a review and restatement of the traditionalview). Until recently, the exception to this dominant view of anterior cerebralstructures as the culmination of the processing cascade was to be found inCricks (1984) hypothesis for a neural mechanism underlying attention.The purpose of this text is to question the validity of the conventionalsolution. I doubt that there is a unidirectional cascade. I also question theinformation-processing metaphor implicit in the solution, that is, the notionthat finer representations emerge by progressive extraction of features, andthat they flow caudo-rostrally. Specifically, we believe that by using this viewof brain organization and function the experimental neuropsychological find-ings in patients with agnosia and amnesia become unmanageably paradoxical.I also suggest that there is a lack of neuroanatomical support for some re-quirements of the traditional view, and that there are neuroanatomical find-ings to support an alternative model. Finally, I believe that availableneurophysiological data can be interpreted to support the alternative theoryI propose.Paradoxes and contradictions for the traditional solutionObjections from human studies with the lesion methodIf temporal and frontal integrative cortices were to be the substrate for theintegration of neural activity on the basis of which perceptual experience andits attempted recall unfold, the following should be found:(a) That the bilateral destruction of those cortices should preclude theperception of reality as a coherent multimodal experience and reduce experi-Neural substrates of recall31ence to disjointed, modality-specific tracks of sensory or motor processing tothe extent permitted by the single modality association cortices;(b) That the bilateral destruction of the integrative cortices should reducethe quality of even such modality-specific processing, that is, reduce the rich-ness and detail of perception and recall commensurate with the quality ob-tainable by the level of non-integrative stations left intact;(c) That the bilateral damage to the rostra1 integrative cortices should dis-able memory for any form of past integrated experience and interfere withall levels and types of memory, including memory for specific entities andevents, even those that constitute the perceivers autobiography, memory fornon-unique entities and events, and memory for relationships among fea-tures, entities, and events.The results of bilateral destruction of the anterior temporal lobes, either inthe medial sector alone or the entire anterior temporal region, as well asbilateral destruction of prefrontal cortices, either in separate sectors or incombination, deny all but a fraction of one of these predictions.Evidence from anterior temporal cortex damageIt is not true that coherent, multimodal, perceptual experience is disturbedby bilateral lesions of the temporal integrative units, and it is not true thatthose lesions cause the perceptual quality of experience to diminish. On thecontrary, all available evidence indicates that at both consciously reportableand non-conscious covert levels, the quality of perceptual experience of sub-jects who have sustained major selective damage to anterior temporal corticesis comparable to controls (see Corkin, 1984; Damasio et al., 1985a,b, 1987).Such subjects can report on what they see, hear, and touch, in ways thatobservers cannot distinguish from what they themselves see, hear, and touch.A variety of covert knowledge paradigms (e.g., forced recognition and pas-sive skin conductance) indicates that they can also discriminate stimuli, prob-ably on the basis of non-conscious activation of detailed knowledge about theitems under scrutiny (Bauer, 1984; Tranel & Damasio, 1985, 1987, 1988).More importantly, the knowledge that such subjects can evoke consciously,at a non-autobiographical level, indicates that ample memory stores of inte-grated experience remain intact after damage to the alleged integrative units.These facts support the contentions: (1) that a considerable amount of inte-gration must take place early on in the system well before higher-order corticesare reached; (2) that integrated information can be recorded there withoutthe agency of rostra1 integrative units; and (3) that it can be re-evoked theretoo, without the intervention of rostra1 integrative structures.32A. R. DamasioThe only accurate prediction regarding the role of alleged integrative unitsapplies to anterior temporal cortices and concerns the loss of the ability torecall unique combinations of representations that were conjoined in experi-ence within a specific time lapse and space unit. That ability is indeed lost,along with the possibility of creating records for new and unique experiences.This is exemplified by the neuropsychological profile of the patient Boswell,whose cerebral damage entirely destroyed, bilaterally, both hippocampal sys-tems (including the entorhinal cortex, the hippocampal formation, and theamygdala), the cortices in anterolateral and anteroinferior temporal lobes(including areas 38, 20, 21, anterior sector of 22, and part of 37), the entirebasal forebrain region bilaterally (including the septal nuclei, the nucleusaccumbens and the substantia innominata, which contains a large sector ofthe nucleus basalis of Meynert), and the most posterior part of the orbitofron-tal cortices. Boswells perception in all modalities but the olfactory is flawlessand the descriptions he produces of complex visual or auditory entities andevents are indistinguishable from those of his examiners. All aspects of hismotor performance are perfect. His use of grammar, his phonemic andphonetic processing, and his prosody are intact. His memory for most entitiesis preserved, and at generic/categorical levels his defect only becomes evidentwhen subordinate specificity is required for the recognition of uniqueness orfor the disambiguation of extremely similar exemplars. For instance, he rec-ognizes virtually any man-made object such as a vehicle, tool, utensil, articleof furniture or clothing, but cannot decide whether he has previously encoun-tered the specific exemplar, or whether or not it is his. Although he canrecognize the face of a friend as a human face, or his house as a house, andprovide detailed descriptions of the features that compose them, he is unableto conjure up any event of which the unique face or house was a part, andwhich belong to his autobiography. In short, his essential perceptuomotorinteraction with the environment remains normal provided uniqueness ofrecognition, recall, or action are not required. Recognition, recall, and imag-ery operate as they should for large sectors of knowledge at the generic/categorical level.Evidence from anterior frontal lobe damageDamage to bilateral prefrontal cortices, especially those in the orbitofrontalsector, is compatible with normal perceptual processes and even with normalmemory for entities and events, except when they pertain to complex domainssuch as social knowledge (Damasio & Tranel, 1988; Eslinger & Damasio,1985). Bilateral lesions in superior mesial and in dorsolateral cortices causedefects in drive for action, attention, and problem solving, that may secondar-Neural substrates of recall33ily influence perceptual tasks. However, even extensive ablation of virtuallythe entire prefrontal cortices is compatible with normal perception. The studyof Brickners patient A, of Hebbs and Ackerly and Bentons patients (seeDamasio, 1985b for a review), and of our subject EVR (see Eslinger &Damasio, 1985) provides powerful evidence in this regard. Frontal lobe struc-tures, with their multiple loci for the anchoring of processing cascades(Goldman-Rakic, 1988), are even less likely candidates to be the single,global site of integration than their temporal counterparts.Evidence from damage in single-modality corticesPerhaps the most paradoxical aspect of these data, when interpreted in lightof the traditional view, is that damage in certain sectors of sensory associationcortices does affect the quality of some aspects of perception within the sen-sory modality of those cortices. For instance, damage in early visual associa-tion cortices can disrupt perception of color, texture, stereopsis, and spatialplacement of the physical components of a stimulus. The range of loss de-pends on which precise region of visual cortex is most affected (Damasio,1985a).The perceptual defect is accompanied by an impairment of recall and rec-ognition. For instance, achromatopsia (loss of color perception) also pre-cludes imaging color in recall (Damasio, 1985; Farah, 1989 and unpublishedobservations), that is, no other cortices, and certainly no other higher-order,integrative cortices, are capable of supporting the recall of the perceptuallyimpaired feature. The coupling of perceptual and recall impairments is strongevidence that the same cortices support perception and recall. This finding,based on lesion method studies, is in line with evidence from normal humanexperiments (Kosslyn, 1980). It also suggests an economical approach tobrain mapping of knowledge that might obviate the problem of combinatorialexplosion faced by the traditional view. In my proposal, the brain would notre-inscribe features downstream from where it perceives them. Furthermore,damage within some sectors of modal association cortices can disturb recalland recognition of stimuli presented through that modality, even when basicperceptual processing is not compromised. The domain of stimuli, and thetaxonomic level of the disturbance, depend on the specification of the lesionin terms of site, size, and uni- or bilaterality (Damasio & Tranel, 1989; seealso work on category-related recognition defects reviewed in Damasio, 1989;and McCarthy & Warrington, 1988). Lesions within visual association corticesmay impair the recognition of the unique identity of faces, while allowing forthe recognition of facial expressions, non-unique objects, and visuo-verbalmaterial. Or lesions may compromise object recognition and leave face recog-34A. R. Damasionition untouched (Feinberg, Rothi, & Heilman, 1986; Newcombe & Ratcliff,1974), or compromise reading but not object or face recognition (Damasio& Damasio, 1983; Geschwind & Fusillo, 1966). The key point is that damagein a caudal and modal association cortex can disrupt recall and recognition ateven the most subordinate taxonomic level. It can preclude the kind of inte-grated experience usually attributed to the rostra1 cortices, that is, an evocationmade up of multiple featural components, based on different modalities,constituting entities and events. This can happen without disrupting percep-tion within the affected modality and without compromising recall or recog-nition in other modalities. Damage in modal cortices also disrupts learningof new entities and events presented through the modality (Damasio et al.,1989a).These findings indicate that a substantial amount of perceptual integrationtakes place within single-modality cortices, and that knowledge recalled atcategoric levels (also known as semantic, or generic) is largely dependent onrecords and interactions among posterior sensory cortices and the intercon-nected motor cortices.It also indicates that recall and recognition of knowledge at the level ofunique entities or events (also known as episodic) requires both anterior andposterior sensory cortices, an indication that a more complex network isneeded for intricate subordinate-level mappings and that anterior integrativestructures alone are not sufficient to record and reconstruct knowledge atsuch levels.The implications are:(a) that the posterior sensory cortices are sites where fragment records areinscribed and reactivated, according to appropriate combinatorial arrange-ments (by fragments I mean parts of entities, at a multiplicity of scales,most notably at the feature level, for example color, movement, texture, andshape); such cortices are also capable of binding features into entities andthus re-enact the perceptual experience of entities and their operations(local or entity binding). But posterior cortices cannot map non-localcontextual complexity at event level, which is to say they cannot map the spatialand temporal relationships assumed by entities within the multiple concurrentevents that usually characterize complex interactions with the environment.(b) the inscription of contextual complexity, that is, the complexity of theThe terms semantic and episodic were proposed by Tulving (1972). Our term generic is largely equivalentto semantic and categorical. Elsewhere in the text I refer generic or categorical knowledge as supraordinateor basic object level knowledge, and to episodic knowledge as subordinate level knowledge. The latterterms are drawn from Roschs nomenclature for taxonomic levels (Rosch et al., 1976).Neural substrates of recall 35combinatorial arrangement exhibited by many concurrent events (non-localor event binding), requires anterior cortices, although its re-enactment alsodepends on posterior cortices.The posterior cortices contain all the fragments with which experiences canpotentially be reconstituted, given the appropriate combinatorial arrange-ment (binding). But as far as combinatorial arrangements are concerned, theposterior cortices contain primarily the records for local entity or simpleevent binding. They do not contain records for non-local concurrent eventbinding and are thus unable to reconstitute experiences based on the contex-tually complex, multi-event situations that characterize ones autobiography.The anterior cortices do contain such non-local, concurrent event bindingrecords. The critical point is that since posterior cortices contain both frag-ment and local binding records, they are essential for all experience-replica-tive operations. Anterior cortices are only required to assist experiences thatdepend on high-level contextual complexity.I would predict, based on the above hypotheses, that simultaneous damagein strategic regions of several single-modality cortices, for example visual,auditory, somatosensory, in spite of intactness of the so-called rostra1 integra-tive cortices, would preclude recognition and recall of a sweeping range ofstimuli defined by features and dimensions from those modalities, both atgeneric and episodic levels. The central premise behind my proposal, then,is that extensive damage in early sensory cortices is the only way of produc-ing the effect normally posited for destruction of the anterior units, namelythe suspension of multimodal recognition and recall, from which would followthe abolition of experiences.A testable hypothesis drawn from this premise is that damage in inter-mediate cortices (cortices in parts of areas 37, 36, 35, and 39 that constitutevirtual choke points for the feed-forward-feedback projections that inter-lock earlier and higher-order cortices) should have a comparable disruptingeffect. There is preliminary evidence that this is so from findings on patientswith lesions in these areas (Damasio et al., unpublished; Horenstein, Cham-berlin, & Conomy, 1967), and a study is currently under way to analyzeadditional evidence.Neuroanatomical and neurophysiological evidenceLeaving aside the fact that no bilateral lesion in a presumed anterior integ-rative cortex is capable of precluding coherent perception of any entity orevent, or categorical recall, one might turn around and pose a purelyneuroanatomical question: which area or set of areas could possibly function36A. R. Damasioas a fully encompassing and single convergence region, based on what iscurrently known about neural connectivity? The simple answer is: none. Theentorhinal cortex and the adjacent hippocampal system (hippocampal forma-tion and amygdala) do receive connections from all sensory cortices, andcome closest to the mark. Prefrontal cortices, inasmuch as one can envisagetheir connectivity from neuroanatomical studies in non-human primates, donot fit the bill either. They have no single point of anatomical convergenceequivalent to the entorhinal cortex, only separate convergence points withdifferent and narrower admixtures of innervation. The hypothesis suggestedby these facts is that the integration of sensory and motor activity necessaryfor coherent perception and recall must occur in multiple sites and at multiplelevels. A single convergence site is nowhere to be found.In fact, developments in neuroanatomy and neurophysiology have em-phasized the notion of segregation while beginning to reveal different pos-sibilities for integration. For instance, Hubel and Livingstone (1987) andLivingstone and Hubel(1984) have demonstrated that separate cellular chan-nels within area 17 are differently dedicated to the processing of color, formand motion. Beyond area 17 the evidence shows:(1) Early channel separation and divergence into several functional regionsrevealed by neurophysiological studies (Allman, Miezin, & McGuinness,1985; Hubel & Livingstone, 1987; Livingstone & Hubel, 1984; Van Essen &Maunsell, 1983), and characterized in part by studies of connectivity (Gilbert,1983; Livingstone & Hubel, 1987a; Lund, Hendrickson, Ogren, & Tobin,1981; Rockland & Pandya, 1979, 1981). This form of organization is describ-able by the attributes divergent, one-to-many, parallel, and sequential.(2) The existence of back-projections to the feeding cortical origin, capableof affecting processing in a retroactive manner, and capable of cross-project-ing to regions of the same level (Van Essen, 1985; Zeki, 1987, personalcommunication). This anatomical pattern opens the possibility for variousforms of local integration.(3) Existence of convergence into functional regions downstream (projec-tions from visual, auditory, and somatosensory cortices) can be encounteredin combinations from two and three modalities, in progressively more rostra1brain regions such as areas 37, 36, 35, 38, 20 and 21 (Jones & Powell, 1970;Seltzer & Pandya, 1976, 1978; Pandya & Yeterian, 1985),2 a design featureThe human areas 37 (mesially), 36, and 35 largely correspond to fields TF and TH in the monkey, andto fields TF and TH of van Economo and Koskinas in the human. They are extremely developed in the human,especially area 37. Area 38 corresponds to TG; areas 20 and 21 to TE. Area 39 (the angular gyrus) alsorepresents a major human development and may correspond to expansion of cortices in both posterior superiortemporal sulcus and inferior parietal lobule. Area 40 (the supramarginal gyrus) is largely a new human area.Neural substrates of recall 3’7describable by the attributes convergent, many-to-few, parallel, and sequen-tial. In humans, judging from evidence in non-human primates, trimodalcombinations are likely to occur in functional regions within Brodmannsareas 37, 36, 35, 38, 39; bimodal combinations are likely in areas 40, 20 and21.(4) Existence of further feedback from the latter cortices, that is, con-vergence regions, have the power to back-project divergently to the feedingcortices.The pattern of forward convergence and retrodivergence is repeated in therostra1 cortices of the entorhinal and prefrontal regions. For instance, neuronensembles in higher-order cortices project into the circumscribed clustersfound in layer II and superficial parts of layer III of the entorhinal cortex(Van Hoesen, 1982; Van Hoesen & Pandya, 1975a,b; Van Hoesen, Pandya,& Butters, 1975). I describe this design feature as convergent, and few-to-fewer. Convergence continues into the hippocampal formation proper, bymeans of perforant pathway projections to the dentate gyrus and of projec-tions from there into CA3 and CAl. Convergence is again followed by diver-gent feedbacks via several anatomical routes: (1) a direct route, using thesubiculum and layer IV of the entorhinal cortex, diverges into the corticesthat provide the last station of input into the hippocampus (Kosel, VanHoesen, & Rosene, 1982; Rosene & Van Hoesen, 1977); as noted above,those cortices project back to the previous feeding station; (2) an indirectroute, so far only revealed in rodents but possibly present in primates, whichfeeds back into virtually all previous stations, divergently and in saltatoryfashion, rather than in recapitulatory manner (Swanson & Kohler, 1986); (3)an even less direct and specific route, which uses pathways in the fornix andexerts influence over thalamic, hypothalamic, basal forebrain, and frontalstructures, all of which in turn, directly and indirectly, can influence theoperation of the cerebral cortices in widespread fashion. The latter routeprovides the cortex with regionally selective or widespread neurochemicalinfluence (e.g.,acetylcholine, norepinephrine, dopamine, and serotonin)based on the activity of neurotransmitter nuclei in basal forebrain andbrainstem (Lewis et al.,1986; Mesulam, Mufson, Levey, & Wainer, 1983).The findings clearly indicate that the hippocampus-bound projection sys-tems point as much forward as backward. Furthermore, the convergencenoted anteriorly is always partial, never encompassing the full range of sen-sory and motor processes that may be involved in complex experiences. Pre-cisely the same argument could be presented for the multiplicity of prefrontalcortices that serve as end-points for projections from parietal and temporalregions. The feed-forward projections remain segregated among parallel38A. R. Damasiostreams and are reciprocated by powerful feedbacks to their originating cor-tices or their vicinity (Goldman-Rakic, 1988).The fact that the receptive fields of neurons increase dramatically in acaudal-rostra1 direction has implicitly supported the notion of rostra1 integra-tion. A look at this issue in the visual system reveals that the size of thereceptive field of neurons in area 17 (V,) is extremely small; it enlarges byas much as one hundred times at the level of V,, and at the level of thehigher-order cortices of areas 20 and 21 virtually encompasses the entirevisual scene (Desimone, Schein, Moran, & Ungerleider, 1985). This gradualenlargement of receptive fields, all the way from small and lateralized tolarge and bilateral, has been viewed as an indication that anteriorly placedneurons not only see more of the world but represent a finer picture of it(Desimone & Ungerleider, 1989, Perrett et al., 1987). However, nothing inthose data indicates that the fewer and fewer neurons that are linked to larger andlarger receptive fields contain any concrete representation whatsoever of theperceptual detail upstream or that those neurons are committed and theend-point of multiple-channel processing. Those data are certainly compati-ble with the proposal I present below: (a) that fewer and fewer neuronsplaced anteriorly in the system are projected on by structures upstream andthus subtend a broader compass of feed-forwarding regions; (b) that theyserve as pivots for reciprocating feedback projections rather than as the reci-pients and accumulators of all the knowledge inscribed at earlier levels; and(c) that in such a capacity they are intermediaries in a continuous processthat systematically returns to early cortices.The unavoidable conclusion is that, while it is possible to conceive of theintegration of sensory processes within a few neuronal regions necessary todefine a single entity, it is apparent that no single area in the human brainreceives projections from all the regions involved in the processing of anevent. More importantly, it is inconceivable that any single region of thebrain might integrate spatially all the fragments of sensory and motor activitynecessary to define a set of unique events. An answer to this puzzle, namelythe ability to generate an integrated experience in the absence of any meansto bring the experiences components together in a single spatial meetingground, might be a trick of timing. It would allow the perceiver or recallerto experience spatial integration and continuity in relation to sets of activitythat are spatially discontinuous but do occur in the same time window, anillusory intuition.Neural substrates of recall 39A different solutionFollowing on the evidence and reflections outlined above and incorporatingadditional neuropsychological and neuroanatomical data, I propose the fol-lowing solution:(a) The neural activity that embodies physical structure representationsentity occurs in fragmented fashion and in geographically separate corticeslocated in modal sensory cortices. The so-called integrative, rostra1 corticesof the anterior temporal and prefrontal regions cannot possibly contain suchfragmentary inscriptions.(b) The integration of multiple aspects of reality, external as well as inter-nal, in perceptual or recalled experiences, both within each modality andacross modalities, depends on the time-locked co-activation of geographi-cally separate sites of neural activity within sensory and motor cortices, ratherthan on a neural transfer and integration of different representations to-wards rostra1 integration sites. The conscious experience of those co-acti-vations depends on their simultaneous, but temporary, enhancement (herecalled co-attention), against the background activity on which other activa-tions are being played back.(c) The representations of physical structure components of entities arerecorded in precisely the same neural ensembles in which corresponding ac-tivity occurred during perception, but the combinatorial arrangements (bind-ing codes) which describe their pertinent linkages in entities and events (theirspatial and temporal coincidences) are stored in separate neural ensemblescalled convergence zones. The former and the latter neuron ensembles areinterlocked by reciprocal projections.(d) The concerted reactivation of physical structure fragments, on whichrecall of experiences depends, requires the firing of convergence zones andthe concomitant firing of the feedback projections arising from them.(e) Convergence zones bind neural activity patterns corrseponding to to-pographically organized fragment descriptions of physical structure, whichwere pertinently associated in previous experience on the basis of similarity,spatial placement, temporal sequence, temporal coincidence, or any combi-nation of the above. Convergence zones are located throughout the telen-cephalon, at multiple neural levels, in association cortices of different or-ders, limbic cortices, subcortical limbic nuclei, and non-limbic subcorticalnuclei such as the basal ganglia.(f) The geographic location of convergence zones varies among individualsbut is not random. It is constrained by the subject matter of the recordedmaterial (its domain), by degree of contextual complexitiy in events (the40A. R. Damasionumber of component entities that interact in an event and the relations theyadopt), and by the anatomical design of the system.(g) The representations inscribed in the above architecture, both thosethat preserve topographic/topologic relationships, and those that code fortemporal coincidences, are committed to populations of neuron ensemblesand their synapses, in distributed form.(h) the co-occurrence of activities at multiple sites, which is necessary fortemporary conjunctions, is achieved by iteration across time phases.Thus I propose not a single direction of processing, along single or multiplechannels, but rather a recursive and iterative form of processing. Such pro-cessing is parallel and, because of the many time phases involved in multiplesteps, it is also sequential. Convergence zones provide integration, and, al-though the convergence zones that realize the more encompassing integrationare more rostrally placed, the activities that all levels of convergence zoneend up promoting, and on the basis of which representations are reconstitutedand evoked, actually take place in caudal rather than rostra1 cortices. Andbecause convergence zones return the chain of processing to earlier corticeswhere the chain can start again towards another convergence zone, there isno need to postulate an ultimate integration area. In other words, thismodel can accommodate the astonishing segregation of processing streamsthat the work of Livingstone and Hubel has revealed so dramatically.The sensory and motor cortices are thus seen as the distributed and yetrestricted sector of the brain on which both perception and recall play them-selves out, and on which self-consciousness must necessarily be based. Per-ception and self-consciousness are assigned the same brain spaces at the bor-der between the world within and the world without.In the following section I present a framework based on these views anddiscuss its structures, systems, organization, and operation.Timelocked multiregional retroactivation: framework, structures, systemsorganization, and operationFrameworkBecause of its origin in mutually constraining sets of cognitive and neuraldata, the theory developed here is both cognitive and neural. The cognitivearchitecture implicit in the theory assumes representations that can be de-scribed as psychological phenomena and interrelated according to combinato-rial semantics and syntax. The proposed neural organization, however, is notNeural substrates of recall 41a mere hardware implementation apparatus for any potential type of cogni-tive processes, in that its specifications severely restrict the range of represen-tations and algorithms that it can implement; that is, it is not likely to imple-ment representations other than the ones its anatomy and physiology embodyand are destined to operate. The key level of neural architecture is that ofsystems of macroscopic functional regions in cerebral cortex and gray matternuclei.The theory describes an adult neural/cognitive organization presumed to berelatively stable and yet modifiable by experience, to produce temporary orlong-lasting partial reorganizations. The issues of neural and cognitive de-velopment are not addressed, nor does the theory deal with microneuralspecifications at synaptic and molecular levels. However, it does assume thatany inscription of perceptuomotor activity is based on a distributed transfor-mation of physiological parameters, occurring over ensembles of neurons atthe level of their synapses, according to some variant of Hebbian principles.The theory operates on the basis of neurobiological and reality constraints.Neurobiological constraintsThese correspond to the structural design of the nervous system prior tointeractions with the environment: the basic circuitry of cellular structuresand their interconnectivity, which can be changed by epigenetic interactions.The design includes neuroanatomically embodied values of the organism(e.g., goals and drives of the species), external and internal spatial referencemaps, and a variety of processing biases that are likely to guide, in part, themapping of interactions with the environment, that is, the domains of knowl-edge that the brain prefers to acquire and the choice of neural sites to supportsuch knowledge. The effect of these constraints is to provide a certain degreeof innate modularization of faculties upon exposure to the reality con-straints discussed below.Reality constraints: the world without and the world withinThe description of the characteristics of the universe surrounding the brain,both inside and outside the organism, can be made at the multiple levels thatcurrent knowledge of philosophy, psychology, physics, chemistry, and biol-ogy permit. From my point of view, however, it is sensible to focus thedescription on the levels from which we derive psychological meaning: (1) abroad range of objects to which I will refer to as entities and which encompassboth natural and man-made kinds; (2) the features and dimensions that com-pose those entities; and (3) the interplay of entities in unique events or42A. R. Damasioepisodes occurring in temporal and spatial units. Thus, the set of realityconstraints corresponds to:(1) The existence of concrete entities external to both brain and organism,and external to the brain but internal to the organism (somatic). Externalentities are themselves composed of various aggregated features and dimen-sions in an entity-intrinsic space (the space defined by the physical limits ofthe entity) and are, in turn, placed within an entity-extrinsic space (the coor-dinate space where the entity and other entities lie or move). Internal entitiesconsist of: (a) motor interactions of the organism with external entities bymeans of movements in hands, head, eyes, and whole body; (b) baselinesomatic states of internal milieu and of smooth and striated musculatureduring interaction with external entities; and (c) modification of somaticstates triggered by and occurring during interaction with external entities.(2) The existence of abstract entities are criterion-governed conjunctionsof features and dimensions present in the concrete entities outlined above.(3) The fact that entities necessarily occur in unique interactive combina-tions called events, and that events often take place concurrently, in complexsets.Entities are definable by the number of components, the modality range ofthose components (e.g., single or multiple modality), the mode of assembly,the size of the class formed on the basis of physical structure similarity, theiroperation and function, their frequency of occurrence, and their value to theperceiver.As is the case with entities, events can be both external and internal, andboth concrete and abstract. The concurrence of many events which charac-terize regular life episodes generates contextual complexity, which can bedefined by the number of entities and by the relational links they assume asthey interplay in such complex sets of events. Naturally, during the unfoldingof events, other entities and events are recalled from autobiographical re-cords. The records co-activated in that process add further to the contextualcomplexity of the experiences that occur within a given time unit. It is thuscontextual complexity which sets entities and events apart and which confersgreater or lesser uniqueness to those entities and events. In other words,contextual complexity sets the taxonomic level of events and entities along acontinuum that ranges from unique (most subordinate) to non-unique (lesssubordinate and more supraordinate).Neural substrates of recall 43Domain formation and recording of contextual complexityDuring interactions between the perceivers brain and its surround, the twosets of constraints lead to some critical operations that can be described asfollows from a psychological standpoint:(1) domain formation, which is a process of feature, entity, and event group-ing based on physical structure similarity, spatial placement, temporalsequence, and temporal coincidence;(2) the creation of records of contextual complexity that register the tem-poral coincidence of entities and their interrelationships within sets ofevents.It is on the basis of this psychological-level description and on the evidencethat category-related recognition defects can be associated to damage inspecific brain loci that we hypothesize neural substrates for different knowl-edge domains and levels of knowledge processing. It must be noted that forthe purposes of modeling we are here inverting the natural order of things:domains exist because of neurobiological and reality constraints, not the otherway around.Functional regionalizationThe process of regionalization occurs for both fragments of perceptuomotoractivity and convergence zones. I conceive it as a way of recruiting a neuronpopulation for a limited range of cortical inputs (and, by extension, to thedomain or level defined by the feed-forwarding neuronal populations). Inother words, certain topics (at feature, entity, or event level) are assigned toa circumscribed neuronal population. Within that polulation, however, differ-ent synaptic patterns define individual features, or entities, or events. Insimple terms one might say that generally similar material stacks up togetherwithin the same regions and systems.As I will discuss further on, the superimposed, overlapped nature of therecords poses problems for their appropriate separation during recall. The solu-tion I envisage, and that may appear counterintuitive at first glance, resides withthe wealth and complexity of the record at the synaptic level. The greater thenumber of defining sub-components and distinctive links, the greater thechance of establishing uniqueness at the time of recording and at the time ofreactivation.The key to regionalization is the detection, by populations of neurons, ofcoincident or sequential spatial and temporal patterns of activity in the inputneuron populations. Precisely the same type of neuron ensembles, operating44A. R. Damasioon precisely the same principles, will constitute the substrate for differentcognitive operations depending on the location of the ensemble within thesystem and the connections that feed into the ensemble and that feed backout of it. In other words, location and communication lines determine thetopic of the synaptic patterns within a given neuron ensemble (the domainof a convergence zone), without there being a need to posit special neurontypes or special physiological codes in order for convergence zones to servedifferent domains or cognitive operations.The nature of representationsHuman experiences as they occur ephemerally in perception are the result ofmultiple sensory and motor processing of a collection of features and dimen-sions in external and internal entities. Specifically they are based on thecerebral representation of concrete external entities, internal entities,abstract entities, and events.Such representations are interrelated by combinatorial arrangements sothat their internal activation in recall and the order with which they areattended, permits them to unfold in a sentential manner. Such sentencesembody semantic and syntactic principles.In my view, the words of any language are also concrete external entities.The combinatorial semantics and syntax of thought and language might beembodied in the relationships that describe the constitution of entities andevents (although the universal grammar behind language may be based onadditional language-specific principles and rules).This cognitive/neural architecture implies a high degree of sharing andembedding of representations. Both the representation of abstract entitiesand of events are derived from the representation of concrete entities andare thus individualized on the basis of combinatorial arrangement rather thanremapping of constituents. The representation of concrete entities themselvesshare subrepresentations of component features so that individuality is againconferred by combinatorial formulas.Human experiences, as they occur ephemerally in recall, are based onrecords of the multiple-site and multiple-level neural activities previouslyengaged by perception. Recalled experiences constitute an attempted recon-struction of perceptual experience based on activity in a set of pertinentsensory and motor cortices, controlled by a reactivation mechanism specifiedbelow.Neural substrates of recall45The components of representationsFeature-based fragmentsI propose that the experienceable (conscious) component of representa-tions results from an attempt at reconstituting feature-based, topographic ortopologically organized fragments of sensory and motor activity; that is, onlythe feature-based components of a representation assembled in a specificpattern can become a content of consciousness. The maximal size of thefeature-based fragment is a critical issue. Stimuli such as human faces, verballexical entities, and body parts of the self, must be permanently representedby large-scale fragments on the basis of which rapid reconstitution can occur.It is unlikely that such stimuli would depend on a reconstruction from thesmallest-scale level of neural activity (equivalent, for the visual system, toBela Julesz textons, 1981). But many fragments are small-scale and can beshared by numerous entities and used interchangeably in the reconstitutionattempt.Convergence zones1. The structure and role of convergence zonesBecause feature-based fragments are recorded and reactivated in sensoryand motor cortices, the reconstitution of an entity or event so that it resem-bles the original experience depends on the recording of the combinatorialarrangement that conjoined the fragments in perceptual or recalled experi-ence. The record of each unique combinatorial arrangement is the bindingcode, and it is based on a device I call the convergence zone.Convergence zones exist as synaptic patterns within multi-layered neuronensembles in association cortices, and satisfy the following conditions: (1)they have been convergently projected upon by multiple cortical regions ac-cording to a connectional principle that might be described as many-to-one;(2) they can reciprocate feed-forward projections with feedback projection(one-to-many); (3) they have additional, interlocking feed-forward/feedbackrelations with other cortical and subcortical neuron ensembles. The signalsbrought to convergence zones by cortico-cortical feed-forward projections,represent temporal coincidences (co-occurrence) or temporal sequences ofactivation in the feeding cortices (rather than re-representations of inscrip-tions contained in the feeding cortices). I envision the binding code as asynaptic patternof activity such that when one of the projections which feed-forward to it is reactivated, firing in the convergence zone leads to simultane-ous firing in all or most of the feedback projections which reciprocated the46 A. R. Damasiofeed-forward from the original set. By means of those reciprocating feedbacklines, convergence zones can trigger simultaneous activity in all or part of theoriginally feeding cortices, in a retroactive and divergent manner, accordingto certain principles of operation specified below. The proposal does notaddress the issue of the number or size of convergence zones, although itassumes that the zones size is defined during development as a result ofinput-output connection patterns, and the patterns of lateral interaction thathelp structure the ensemble as a unit.Convergence zones are amodal, in that they receive signals from the sameor different modalities but do not map sensory or motor activity in a way thatpreserves feature-based, topographic and topological relations of the externalenvironment as they appear in psychological experience. Convergence zonesdo not embody a refined representation, in the sense that would be assumedin an information-processing model, although they do route information in thesense of information theory. They know about neural activity in the feedingcortices and can promote further cortical activity by feedback/retroactivation.In themselves, however, they are uninformed as to the content of the rep-resentations they assist in attempting to reconstruct. The role of convergencezones is to enact formulas for the reconstitution of fragment-based momen-tary representations of entities or events in sensory and motor cortices-theexperiences we remember.32. Operating principlesConvergence zones signal the related binding of the similarity, spatialplacement, temporal sequence,or temporal coincidence of feature-basedfragments highlighted in the perceivers experience. Convergence zonesprompt sensory and motor co-activation by means of back-projections intocortices located upstream. In the extreme view (a mere caricature), all thatwould be required of a convergence zone would be to function as a pivot,that is, to cause retroactivation in sites that it fed back to, after a thresholddefined by concurrent inputs had been reached. The general operating prin-ciple would be stated as: (a) reactivate itself when fired upon; (b) reactivationpromotes firing toward any site to which there are back-projections, recip-The notion of separating storage of fragments of experience. from storage of a catalogue for their recon-stitution, was inspired by our study of patient Boswell, along with the notion that a unidirectional caudal-ros-tral processing cascade was less likely than a multidirectional, recursive organization. The idea of convergencezones came from reflection on patterns of cortico-limbic projections, especially the multiplicity of parallel andconverging channels, and the progressive size reduction of the neural convergence sites along a caudal-rostra1axis. The pattern of disruption of cortico-limbic and cortico-cortical feed-forward and feedback projections inpatients with Alzheimers disease (see Van Hoesen & Damasio.1987, for a review) provided the blueprintfor the construct.Neural substrates of recall 47rotating feed-forward inputs that generated the synaptic pattern that definesthe zone. But because of superimposition and overlapping of convergencezones within the same neuron population, and of the ensuing high numberof synaptic interactions, the range of back-firing of each convergence zone ismodulated rather than rigid. It depends on the momentary number and na-ture of cortical feed-foward inputs (relative to the total number of possiblefeedback outputs that the zone can have), and on the momentary inputs fromother areas of cortex and from limbic system, thalamus, basal forebrain, andso forth.As a consequence, convergence zones can produce different ranges ofretroactivation in the cortex, depending on the concurrent balances of inputsthey receive. Also, convergence zones can blend responses, that is, produceretroactivation of fragments that did not originally belong to the same expe-riential set, because of underspecification of cortical feed-forward inputs, orhigher-order cortical feedbacks, or subcortical feedbacks. When pathologicalcombinations of input are reached, the zone malfunctions, for example, itmay generate fantastic or psychotic responses, or not operate at all.It is important to note that the lines activated by feedback from con-vergence zones are not rigid. They should be seen as facilitated paths thatmay or may not be travelled depending on the ensemble pattern of synapticinteractions within a population.3. Types of convergence zonesI envisage permanent convergence zones in the cortex and temporary con-vergent zones in limbic structures and basal ganglia/cerebellum, based oncurrent findings regarding the profile of retrograde amnesia following hip-pocampal damage. The domain of the convergence zone is determined by itsimmediate and remote feed-forward inputs which are co-extensive with itsback-projection targets.I propose two types of convergence zones. In Type I, the zone fires backsimultaneously and produces concomitant activations. Type I zones inscribetemporal coincidences and aim at replicating them. Type II convergencezones fire back in sequence, producing closely ordered activations in thetarget cortices. Such zones have inscribed temporal sequences and aim atreplicating them. The time scale for firing from Types I and II convergencezones would be different.Type I convergence zones are located in sensory association cortices of lowand high order, and are assisted in learning by the hippocampal system. TypeII convergence zones are the hallmark of motor-related cortices, and areassisted in learning by basal ganglia and cerebellum.In the normal condition, the two types of convergence zone interlock at48A. R. Damasiomultiple levels so that learning relative to an entity or event recruits bothtypes of convergence zones. Likewise normal recall and recognition involveoperations in both types of convergence zone, even when the triggeringstimulus only activates one type of convergence zone at the outset of theprocess.4. The development of convergence zonesThe placement of convergence zones is partly the result of the geneticallyexpressed neuroanatomical design and partly the result of the sculpting pro-cess introduced by learning. Convergence zones develop in association cor-tices that: (a) receive projections in a convergent manner from a wider arrayof cortices located upstream; (b) can reciprocate projections to the feedingcortices; (c) can project downstream to other cortices and subcortical struc-tures; and (d) can receive a wide array of projections from several subcorticaland motor structures.It is the genetic pattern of neuroanatomical connections that first constrainsthe potential domain of convergence zones. For example, a convergencezone in early visual association cortices cannot possibly bind anything butvisually related activity at the level of component features, whereas a con-vergence zone in anterior temporal cortices can be told about activity relatedto numerous simultaneous events and bind their coincidence. But the ultimateanatomical location and functional destiny of convergence zones is deter-mined by learning, as neuron ensembles become differentially dedicated tocertain types of occurrence in feeding cortices.Convergence zones are created during learning as a result of concurrentactivations in neuron ensembles within association cortices of different order,hippocampus, amygdala, basal ganglia, and cerebellum. The concurrent acti-vations come from convergent feed-forward signals generated by neural activ-ity in: (a) sensory and motor cortices (as caused by perception or recall ofexternal or internal entities); (b) feedback projections from other con-vergence zones in association cortices; (c) direct and indirect feedback projec-tions from convergence zones in limbic cortices and from limbic related nu-clei: (d) direct and indirect feedback projections from basal ganglia, non-motorthalamus, and cerebellum; and (e) local microcircuitry interactions.As noted above, convergence zones have thresholds and levels of response.The activation of a convergence zone depends on its internal constitution,the size, locus, number, and location of sensory and motor representationsites that it subtends. It also depends on the momentary concurrent combina-tion of potential trigger weights, from neural activity related to externallygenerated representations, internally recalled representations, and back-pro-jection from all the neuronal sites listed previously.Neural substrates of recall 495. Superposition of signalsConvergence zones contain overlapping binding codes for many entities andevents. Such rich binding is the source of the widening retroactivation thatpermits recognition and thought processes, and yet its wealth, if unchecked,would eventually result in co-activations bearing only minimal relationshipsto previous specific experiences and on inability to reconstitute unique events.Ultimately, fantastic and cognitively catastrophic combinations would occur,as they do in fact occur in a variety of neuropsychological disorders causedby the neuropathological processes at several levels of the system. In thenormal brain, the constraints that impose specificity of co-evocations dependon concurrent inputs from the following systems: (a) other convergencezones, at multiple neural levels, whose subtended retroactivation providesneural context and thereby helps constrain co-activation; and (b) non-specificlimbic nuclei (basal forebrain and brain stem) activated by antero-temporallimbic units (amygdala, hippocampus).6. AttentionIn a system that produces multiple-site activations incessantly, it is neces-sary to enhance pertinently linked sites in order to permit binding by salientcoincidences. I use the term attention to designate the spotlighting processthat generates simultaneous and multiple-site salience and thus permits theemergence of evocations. Consciousness occurs when multiple sites of activa-tion are simultaneously enhanced in keeping or not with real past experi-ences. (Some psychotic and dementia1 states are possibly examples of simul-taneous enhancement of activations whose combination does not conform toreality; in non-pathological states the same applies to day-dreams). As de-fined here, attention depends on numerous factors and mechanisms. First,there is a code for enhancement of activations that is part of the record ofthe activation pattern it enhances. Type II convergence zones are especiallysuited to this role. Secondly, the state of the perceiver and the context of theprocess play important roles in determining the level of activations. Thereticular activating system, the reticular complex of the thalamus, and thelimbic system mediate such roles under partial control of the cerebral cortex.The evocations that constitute experienced recall occur in specified sensoryand motor cortices, albeit in parcellated fashion. Experienced recall thusoccurs where physical structures of external entities or body states were map-ped in feature fragment manner, notwithstanding the fact that a complexneural machinery made up of numerous other areas of cortex and subcorticalnuclei cooperates to reconstruct the co-activation patterns and enhance them.50A. R. Damasio7. The placement of convergence zonesConvergence zones have different placements within association corticesand other gray matter regions, and varied activation thresholds. There arenumerous levels of convergence zone depending on knowledge domain andcontextual complexity (taxonomic level). The functional regionalization of adomain corresponds to the neural inscription of separate sensory and motoractivities related to features and dimensions of different exemplars. The in-scriptions are naturally superimposed to the extent that the respective fea-tures and dimensions overlap, or coincide in time. The inscriptions are natur-ally contiguous when the respective features or acts they represent occurredin temporal sequence. As superimpositions accrue, categories emerge fromthe blends and mergings of separate exemplars. It is important to note thatfor each separate exemplar to be recalled as an individual entity, it is neces-sary to add contextual complexity to its representation. This is accomplishedby connecting its inscription to the inscription of other entities and events sothat an entirely unique set can be defined. When additional inscriptions arenot linked to create unique or nearly unique sets, the superimposition ofexemplars remains categorical or generic, and recall can reconstitute any onepreviously learned exemplar or else a blend of exemplars. The creation ofrecords of contextual complexity, which code for the temporal entities andevents, is thus critical for recall or recognition at unique (episodic) level.It is important to note that in this perspective the building of categoriesoccurs while inscribing episodes. The system operates so that it always at-tempts to inscribe as much as possible of the entire context. Even if thesystem fails to inscribe the whole episode-or if it does inscribe it, but recallcannot fully reconstitute it-the operation preserves enough of the core in-scription of an entity (or event) for categorization to develop from this andother related inscriptions. The inscription of categories precedes episode in-scription; that is, it is neuroanatomically and neurophysiologically morecaudal. This disposition explains the impairment of episodic memory andpreservation of generic memory following damage to anterior temporal cor-tices.Knowledge of objects, faces, numbers, among many others, created byperceptuomotor interactions, is anatomically and functionally regionalizedin a manner different from classic localizationism of function, but that doesadmit a notable degree of anatomical specialization. This form of specializa-tion does not follow traditional anatomical boundaries such as are known forsensory modalities, or cytoarchitectonic brain areas. Nor does it conform tothe functional centers of traditional neurology. The fragment representationsthat comprehensively describe an entity are dispersed by multiple functionalregions which are, in turn, located in different cytoarchitectonic areas. TheNeural substrates qf recall 51many convergence zones necessary to bind the fragments relationally arelocated in yet other neural sites. The region thus formed obeys anatomicalcriteria dictated by the nature of the entity represented, and by the interactionbetween perceiverand entity, and is secondarily constrained by the potentialofferings of the anatomy. The comprehensive representation of a specificentity or category is distributed not only within a population of neurons butis also distributed in diverse types of neural structure, cortically and subcor-tically. In this proposal, the term localization can only refer to an imaginaryspace defined by neural sites likely to contain convergent zones necessary forthe retroactivation of a given set of entities or events. The borders of such aspace are not only fuzzy but changeable, in the sense that for different instan-tiations of retroactivation of a given entity the set of necessary convergencezones varies considerably.Applications of the frameworkIn the following two sections I discuss briefly the application of this proposalto learning and memory and language.Learning and memory1. The relative segregation of memory domainsThe fact that different neural regions support memory for different do-mains is the reason why striking performance dissociations can occur inhuman amnesia. For instance, after lesions in the hippocampal system, pa-tients retain previously learned perceptuomotor skills (so-called proceduralknowledge) or even learn new ones, while memory and learning for newfaces or objects is no longer possible (Cohen & Squire, 1980; Damasio et al.,1985a,b, 1987; Eslinger & Damasio, 1986; Milner, Corkin, & Teuber,1968). This dissociation occurs because the representations of motor entitiesrely on structures that remain intact in those patients: somatosensory andmotor cortices, neo-striatum and cerebellum. As noted above, the functionalessence behind the system formed by those structures is the recording andre-encactment of temporal sequences and relies on Type II convergencezones.Participation of the hippocampal system is not at all necessary for theacquisition and maintenance of procedural memories, provided they are usedonly at a covert level, and the subject is not required to recollect the factualinformation related to the acquisition of the skill or to the circumstances in52A. R. Damasiowhich the skill has been previously exercised. Conscious recall of the sourceof knowledge requires patency of at least one hippocampal region.By contrast, the weight of recording factual knowledge, in spite of itsdiverse base on sensory and motor activities, relies most importantly on sen-sory cortices and necessitates hippocampal activity. The functional essence inthis system is the recording of neural activity related to physical structure (offeatures, entities, and events), spatial contiguity (of features and entities),and temporal coincidence (of entities and events). Type I convergence zonesin the hippocampal-bound association cortices are required. Perhaps themost dramatic lesion-related dissociation within factual knowledge is the onethat compromises memory for complex social events but spares generalknowledge of entities and events outside of a social context (Damasio &Tranel, 1988; Eslinger & Damasio,1985). Other striking dissociationsabound, however, for different categories of objects, for verbal and non-ver-bal knowledge, and for different types of verbal knowledge (Damasio et al.,1989b).2. Different levels of memory processingIn essence, the distinction between generic and episodic memories is adistinction of processing levels during recall or recognition. We can recall atgeneric levels, with little contextual complexity attached to an entity, nodefinition of uniqueness, and no connection to our autobiography. Or we canrecall at progressively richer episodic levels, with the evocation of greatercontextual complexity and the experience of autobiographic events in whichentities play more specific roles. I believe the brain normally attempts to capturethe maximal complexity of every event, although the stability of the recording ofsuch complexity varies with the value of the event and with the anticipatedneed to recall it.3. The mapping of uniqueness and of entity-centered knowledgeThe critical distinction between generic and episodic knowledge, from thestandpoint of learning, resides with the ability to record temporal coincidence(co-occurrence) of entities within a wide and complex context. It is a matterof magnitude that distinguishes generic from episodic levels of processing,somewhat artificially, along a continuum.When a perceiver interacts with a novel entity, learning consists of record-ing any additional patterns of physical structure, somatic state, or relationalbinding that transpired during the interaction but were not previously re-corded. The same applies to learning of new events.In virtually all instances of learning beyond the early acquisition periodsof infancy and childhood, any new pattern of activity related to perceptionNeural substrates of recall53of new entities and events also evokes multiple and previously stored patternsthat are thus co-experienced with the novel stimuli. Learning does not entailthe recording of all the information contained in a new event. Rather, it callsfor the co-evocation of many physical structures and relations previouslyrecorded for related events, the recording of any novel features that had notbeen recorded before, and the linking of novel records with the pre-existingrecords so that a new specific set is defined and the code for its potentialreconstitution committed to a convergence zone.There is a large sharing of memory records such that the same neuralpatterns can be applied to many entities and events by superimposition andoverlap whenever and wherever their physical structure or relational bindingsare shared. The inscription of a specific entity or event can be made uniqueonly by means of connecting a particular component to others. Such an or-ganization is extremely economical and promotes a large memory capacity.However, it is also prone to ambiguity and an easily disordered operation ifone of its many supporting devices malfunctions. Confusional states and someamnesic syndromes caused by subcortical lesions are an expression of suchmalfunctions. At a milder level, fatigue, sleep deprivation, or distraction cancause the same.4. Neural substrates for learning and memory at systems levelThe critical neural substrate for learning and memory comprises two majorsubsystems: one that interconnects sensory cortices assigned to mapping phys-ical structure and temporal coincidence with the hippocampus; and a secondthat interconnects sensory and motor cortices assigned to mapping temporalsequence with the basal ganglia/cerebellum and the dorsolateral frontal cor-tices. Normal operation of these subsystems is cooperative rather than inde-pendent.The neuroanatomical design of the entorhinal cortex and of the sequenceof cellular regions in the hippocampus to which it projects deserves specialmention. This subsystem provides a set of auto-interacting convergence zonesof great complexity. It is the only brain region in which signals originallytriggered by neural activity in all sensory cortices and in centers for autonomiccontrol can actually co-occur over the same neuron ensembles. As such, thisis the appropiate substrate for a detector of temporal coincidences, the func-tion that I have previously proposed for this system and that I believe to belost in amnesia following hippocampal damage (see Damasio et al., 1985a).Such a function is compatible, in essence, with the type of physiological basisfor learning proposed by Hebb, a presynaptic/postsynaptic coincidencemechanism. It is also compatible with a variety of recent cellular and molecu-lar evidence regarding the phenomenon of long-term potentiation (LTP) and54A. R. Damasiothe role of NMDA-gated calcium channels as detectors of coincidence (seeGustafsson & Wigstrom, 1988, for a review).Once detection of co-occurrence takes place, the region acts via its power-ful feedback system into cortical and subcortical neural stations, to assist inthe creation or modification of convergence zones located in the cortices thatoriginally projected into the entorhinal cortex. It is also apparent that such astructure, especially the autocorrelation matrix of CA3, could store withinitself binding codes of the kind I envisage for convergence zones, capable ofcontent-addressed completion. It appears unlikely, however, that the hip-pocampal complex remains as a storage site for long periods, not only becauseof what that would mean in terms of capacity limits and risk of malfunction,but also because bilateral damage confined to the entorhinal cortex/hip-pocampus appears to cause only limited impairments of retrograde memory(Corkin, 1984), and the same appears to be true of bilateral damage to thehippocampus alone (Zola-Morgan, Squire, & Amaral, 1986). The definitiveaccount on this issue is not available yet. In humans, the left and right hip-pocampi appear to be dedicated to different operations and may also operatedifferently in terms of their long-term role in retrieval.5. Consciousness and self-consciousnessAs previously noted, consciousness emerges when retroactivations attaina level of activity that confers salience. Coincident salient sites of activitydefine a set that separates itself from background activity and emerges, inpsychological terms, as a conscious content on evocation as opposed to non-salient retroactivations that remain covert.Conscious contents are all contents about which one can give testimony,in verbal narrative form, but I wish to distinguish them from the subset ofconscious content we call self-conscious contents. The difference resides withthe notion of self and autobiography. In my view, self-consciousness onlyemerges when conscious contents relative to an ongoing stimulus are experi-enced in the context of pertinent autobiographical data. The distinction is notspecious. Patient Boswell is conscious of his environment and properly recog-nizes the stimuli around him but not in relation to his autobiography.Whether the stimulus is something that he ought to have recognized as un-ique, or something truly new to him, his ability to put it in the perspectiveof his life experience is restricted. His self-consciousness is thus limited andunlike that of perceivers in whom evocations generated by novel percepts areco-attended simultaneously with autobiographical evocations.Neural substrates of recall 55LanguageThe representations related to language, that is, the representations of lexicalentries and grammatical operations, including syntactic rules or principles,phonology, morphology, and semantics which constitute the internalized ormental grammar, are perceived, acquired, and co-activated according to theprinciples articulated for non-verbal entities. As noted above, the frameworkdoes not address the issue of innate versus acquired aspects of language,although from a perspective of biological evolution as well as from the inves-tigation of universal properties of the worlds diverse languages it is likelythat the substrates for combinatorial semantics and syntactical principles arepartly innate.The lexicon and language-specific aspects of the grammar, as cultural ar-tifacts, are a subset of reality characterized by certain physical structures (thephysical phonetic articulatory gestures and resultant acoustic correlates oflinguistic units and structures, that is, phones, phonemes, morphemes, words,phrases, sentences, etc.) and logical relationships (grammatical functions) atmultiple levels. Those external physical structures and relations constitute acorpus of signals capable of symbolizing, in sentential terms, most non-lan-guage aspects of reality at any level. By means of both feature-based physicalfragment representations and binding convergence zones, the brain stores thepotential for reconstituting any lexical entry or relational arrangement that ithas learned, as well as the implicit rules by which novel utterances are producedand comprehended. This would not deny the possibility that highly frequent lex-ical entries would be recorded at large-scale fragment level, for instance, thelevel of an entire word stem, a condition that would be highly adaptive.The brain not only inscribes language constituents but also provides directand dynamic neural links between verbal representations and the representa-tion of non-language entities or events that are signified by language. In otherwords, the brain embodies (materializes) in neural hardware the combinedbiological and cultural bond that culture has assigned between a languagerepresentation (a signifier) and a segment of non-verbal reality (a signified),to borrow Saussures suggestive terminology. It is that neural bond that per-mits the two-way, uninhibitable translation process that can automaticallyconvert non-verbal co-activation into a verbal narrative (and vice versa), atevery level of neural representation and operation.Testing the frameworkThere are fundamentally four approaches to test the validity of the hypoth-eses expressed here. One relies on the lesion method, the approach on which56A. R. Damasiomost of these ideas are based. Small focal and stable lesions in humans withneurological disease can be used to probe neuropsychological predictionsbased on the hypotheses expressed here. Another approach involves the useof positron emission tomography in both normals and patients with focalbrain damage, to explore temporal correlations among different cortical re-gions activated by controlled stimuli. Another approach would involve com-putational modeling and testing of the concept of convergence zone. Finally,it will be possible in experiments using multiple recording from differentcortical sites to test the notion of time-locked activations. For instance, in anexperiment where one would record simultaneously from multiple corticalsites encompassing two sensory modalities, the following should be observed:(1) After a delay compatible with feedback firing, electrical stimulation ofconvergence zones would produce synchronous activity in separate cor-tical sites presumed to contain feature-fragments related to the con-vergence zone.The regions chosen for stimulation would be guided by knowledge ofneurons in association cortex that respond constantly to specific stimuli,for example, faces. Likewise, the choice of areas to guide the search fortime-locked activity in early cortices would come from knowledge ofareas known to be activated by the perception of a specific stimulus, forexample, a face.(2) The lack of finding of time-locked activity across a vast array of corticalregions theoretically presumed to be necessary for the reconstitution ofa perceptual set would constitute evidence against the notion of con-vergence zones proposed here.Situating the proposalI see the following features of the theory as distinctive:(1)(2)(3)The notion that there is a major distinction between records of physicalstructure fragments, and records of combinatorial arrangements amongthose records.The notion that the experience of entities or events in recall alwaysdepends on the time-locked retroactivation of fragmentary records con-tained in multiple sensory and motor regions and thus on momentaryattempted reconstitutions of the once perceived components of reality.The notion that while evocations only exist momentarily, they are theonly directly inspectable aspect of brain activity. Their fleeting existencemakes them no less real. Furthermore, although their existence dependsNeural substrates of recall 57(4)(5)(6)(7)on a complex machinery distributed by multiple brain sites and levels,the proposal specifies that the attempted reconstitutions occur in ananatomically restricted sector of the cerebrum.The notion that certain aspects of the interaction between perceiver andreality generate domains of knowledge, which become regionalized ac-cording to neural constraints rather than conceptual-lexical labels.The notion that the anatomical placement and connectional definitionof a convergence zone, that is, the specification of its inputs and outputsat the point in the system that is located, also defines the knowledgedomain the convergence zone embodies.The role attributed to feedback projections, especially cortico-cortical,in the mechanisms of reconstitution of experiences. Feedback is distin-guished from re-entry as used in the automata of Edelman and Reeke(1982). Feedback and feed-forward carry signals about activity in inter-connected units but they do not transport a movable representationbeing entered or re-entered. Feed-forward signals mark the presence ofactivity upstream in the network, and indicate the whereabouts of re-cords of activity. Feedback reactivates such upstream records. The con-vergence zones record those relationships and operate to route activity.No representations of reality as we experience it are ever transferred inthe system; that is, no concrete contents and no psychological informa-tion move about in the system.The value accorded to representations of internal somatic states in alltheir aspects and levels. Somatic states are generally relegated to a sub-sidiary position, a matter of non-specific influence on the general workingsof a network concerned with representations of external reality. In thisproposal somatic states are memorized in feature-based fragment rec-ords (linked by binding convergence zones), just as external stimuliare. The source for this notion was our studies of humans with focallesions, especially those with conditions such as anosognosia and ac-quired disorders of conduct (Damasio & Anderson, 1989).It is perhaps useful to compare this proposal to other recent proposals thatdeal with cognitive processes and the organization of their putative neuralsubstrates. In order to do this we will choose two reference points: the clas-sical model of cognitive architecture, as presented, for instance, by Fodorand Pylyshyn (1988), and a range of models known under the designationsparallel distributed processing or connectionism (see Rumelhart &McClelland, 1986).We believe that the structures and operations described in this theoryoccupy an intermediate position and are compatible with the proposals in58A. R. Damasiothese reference points. The neural organization we propose is at the level ofsystems formed by macroscopic functional regions. It embodies and can im-plement some predicates of a classical cognitive architecture. On the otherhand, it is conceivable that connectionist nets and alogrithms may realizesome of the microscopic levels underlying the organization proposed here.By the same token our theory is also compatible with neuronal group selec-tion theory (Edelman & Finkel, 1984). Although the specification of neuronunits in those theories is designed in brain-style, the overall networks arenot yet brain-like.The principles of structure and operation of themachines so designed are not aimed at the superstructure organization neces-sary for cognitive processes such as thought, language, or consciousness; thatis, to our knowledge they do not yet compel separate units to hook themselvesup in a particular way capable of making a system thoughtful and self-con-scious. 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Le processus dactivation est dirige a partir de multiples zones de convergence sit&esdarts les cortex dassociation et dans certains noyaux gris sous-corticaux. Les zones de convergence enregistrentde facon amodale larrangement combinatoire des differents fragments de formes tels quil se presente dansles aires corticales precoces au tours de lentite ou de levenement. Les zones de convergence sont reliees avecles ensembles neuronaux primaires par des projections reciproques qui forment des chemins facilites plutotque des liens rigides. Le fonctionnement des zones de convergence est module de facon dynamique par lesentrees concurrentes provenant dautres aims et noyaux sous-corticaux. Ce modele refuse Iexistence dun siteanatomique unique pour lintegration sensori-motrice et dune memoire unique gardant le sens dentites oudevenements. Le sens rtsulte de la retro-activation distribuee et synchrone de fragments. Seuls ces derniersatteignent le seuil du conscient.